Calcium homeostasis Flashcards
Roles of calcium (5)
Signalling - for exocytosis of vesicles, muscle contraction
Blood clotting - essential part of clotting cascade
Apoptosis
Skeletal strength
Membrane excitability - calcium decreases sodium permeability
What effect does hypocalcaemia have on neuronal Na+ permeability
increases Na+ permeability leading to hyper excitation of neurons
What effect does hypercalcaemia have on neuronal Na+ permeability
decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity
Percentage distribution of calcium in the body (divided into 3 places)
Bones - 99%
Intracellular (mainly stored in mitochondria and sarcoplasmic reticulum) - 0.9%
Extracellular fluid - 0.1%
0.1% calcium in the body is distributed in the ECF, how much of this is physiologically active
Only 0.05% as the other 0.05% is bound to carrier proteins like albumin or globulins so is not free in solution
99% of calcium in the body is distributed in bone - how is it stored in bone
in the form of hydroxyapatite, in the extracellular matrix of bone
Conc. of calcium in the plasma (i.e. ECF)
Conc. of physiologically active calcium in the plasma (i.e. free in solution)
- 2-2.6mM (av. 2.4mM)
1. 2mM (as 50% Ca2+ in ECF is unbound, therefore free and ionised)
What minerals does hydroxyapatite consist of (2)
Calcium + phosphate
0.1% calcium that is distributed in the ECF (blood) is further sub-distributed in what 3 ways
40% bound to protein
50% free in solution
10% complexed with anions, e.g. bicarbonate, phosphate, to form calcium carbonate/phosphate etc
The binding capacity of plasma proteins to Ca2+ is affected by what
pH
-binding capacity is increased under alkaline conditions
How does hyperventilation affect the binding capacity of plasma proteins to Ca2+
binding capacity is increased under alkaline conditions so hyperventilating would cause plasma proteins to bind more Ca2+ as hyperventilating means you’re breathing out more CO2 so making blood more alkaline
May lead to hypocalcaemic tetany (involuntary contraction of muscle as neuronal permeability to Na+ is increased so progressive depolarisation)
How does alkalosis increase the binding capacity of plasma proteins to calcium (acidosis therefore opposite)
in alkalosis, protons are deprotonated (i.e. loss of hydrogen ions bound to plasma protein which frees up binding spaces for Ca2+)
so the overall resulting negative charge on the protein allows Ca2+ to bind, thus reducing the amount of ionised calcium whilst total extracellular Ca2+ remains constant
whereas acidosis, there’s increased plasma hydrogen ions so they’d displace the Ca2+ bound to plasma proteins and increase the amount of free ionised Ca2+
The 99% calcium store in bone functions to provide mechanical support but function is prioritised over this
Maintaining Ca2+ balance by releasing its calcium stores into the blood when needed TO MAINTAIN 1.2mM physiologically active plasma calcium
What are osteoblasts + function
Bone building cells
-lay down collagen matrix which then calcifies into bone
What do osteoblasts differentiate into
Osteocytes when established in bone
Function of osteocytes
regulate the activity of osteoblasts and osteoclasts
- much less active than osteoblasts
What are osteoclasts + function
Bone resorbing/destructing cells
- mobilise bone to allow release of its Ca2+ stores
- —-> does this by secreting H+ to dissolve calcium salts and provide proteolytic enzymes to digest the extracellular matrix and release Ca2+ into blood
Explain the overall effect of PTH on plasma Ca2+ and phosphate concentrations
To increase concentration of free plasma Ca2+ (i.e. Ca2+ that is not bound to carrier protein)
Decreases plasma phosphate concentrations which in turn elevates free plasma Ca2+ conc. as it’s prevented from being deposited back into bone, as that process requires phosphate
What is calcitriol + what organs is it produced by
Active form of vitamin D (vitamin D3)
Steroid hormone produced from vitamin D by liver AND kidneys (first step is in liver)
Describe the 5 different mechanisms in which PTH increases free plasma Ca2+ conc.
Stimulates osteoclasts (BONE) to INCREASE RELEASE OF Ca2+ and phosphate into blood
Inhibits osteoblasts to reduce Ca2+ deposition in bone
Increases REABSORPTION OF Ca2+ from KIDNEY tubules, so decreasing its excretion in urine
Increasing RENAL EXCRETION OF PHOSPHATE, which elevates free plasma Ca2+ by preventing it from being deposited back into bone (a process that requires phosphate)
Stimulate the kidney to synthesise CALCITRIOL from vitamin D to promote calcium absorption at the gut and kidney
What relationship does calcitriol have with PTH
It complements the action of PTH to increase plasma Ca2+ conc.
In what 2 ways can be obtain calcitriol (active vitamin D3) (2)
From dietary vitamin D
UV light on skin –> activating endogenous (internal) precursors of vitamin D
Primary action of calcitriol (activated form of vitamin D by kidney) + other actions (2)
Increase Ca2+ absorption form gut by active transport form intestinal lumen into blood
Facilitates renal absorption of Ca2+
Mobilises Ca2+ stores in bone by stimulating osteoclast activity
*Goal of calcitriol is to increase plasma Ca2+ conc. like PTH
Increased levels of PTH stimulate the kidneys to release what
Calcitriol
Calcitriol (active vitamin D3) formation is stimulated when there’s low plasma Ca2+, how else can it be stimulated in women
By prolactin hormone in lactating women
-stimulates kidney to synthesise calcitriol due to increased demand for Ca2+ for milk production
Effect of PTH on renal formation of 1, 25 – dihydroxycholecalciferol (CALCITRIOL)
PTH stimulates release of calcitriol (1, 25 dihydroxycholecalciferol)
Effect of 1, 25 - dihydroxycholecalciferol (CALCITRIOL) on calcium absorption from the gut
Increases Ca2+ absorption from gut
Are circulating levels of calcitriol (1, 25 dihydroxycholecalciferol) low or high in:
- vitamin D deficient individuals
- pregnant/lactating women
+ why
Low - as calcitriol is derived from vitamin D so would be low if little vitamin D
–> due to less dietary Ca2+ absorbed than usual
High - lactating women produce prolactin hormone stimulates kidneys to release calcitriol due to an increased need for Ca2+ in milk production
–> due to more dietary Ca2+ absorbed than usual
If deficient in vitamin D, then deficient in calcitriol so what effect does this have on PTH and plasma Ca2+ conc.
Calcitriol deficiency means decreased intestinal absorption of Ca2+ so decrease in plasma Ca2+ conc. therefore increasing PTH secretion which promotes phosphate deficiency –> aggravating Ca2+ loss from bone
PTH has to work alone to maintain plasma Ca2+ conc. and does so by continually removing Ca2+ from bone which sacrifices bone strength
Vitamin D deficiency can lead to what conditions in children/adults
children - rickets
adults - osteomalacia
Name a hormone that decreases plasma Ca2+ conc. (so unlike PTH and calcitriol)
Calcitonin
What type of hormone is calcitonin + what is it produced by
Peptide hormone
Thyroid gland
Main stimuli of calcitonin
Increased plasma Ca2+ conc.
Acts to decrease this
Mechanisms of calcitonin in decreasing plasma Ca2+ conc. (2)
Bind to osteoclasts and inhibit bone resorption (release into blood)
Increase renal excretion to prevent further increase in plasma Ca2+
Although calcitonin functions to decrease plasma Ca2+ conc. when it’s high, evidence suggests what about its importance in humans
Not that important because if calcitonin levels are very high or if no calcitonin is secreted at all, plasma Ca2+ levels are still normal
So excess calcitonin is OVERRIDDEN BY PTH
In short, what effect does acidosis and alkalosis have on FREE IONISED plasma Ca2+
Acidosis increases free ionised plasma ca2+ - less Ca2+ bound to plasma protein as more H+ bound to them
Alkalosis decreases it - as more Ca2+ bound to plasma protein
Parathyroid glands secrete what
Parathyroid hormone
What 2 cell types is each parathyroid gland made up of
Chief cells
Oxyphil cells
Function of chief cells of the parathyroid glands
produce and secrete PTH in response to low extracellular calcium
How is vitamin D metabolised into a biologically active form (dietary and sunlight vitamin D is inactive)
First hydroxylated by vitamin D hydroxylase into 25-hydroxycholecaiferol (calcidiol), which is the major circulatory form of the vitamin
then
converted in kidney into 1,25-dihydroxycholecalciferol (CALCITRIOL) - biologically active
